TY  - JOUR
AU  - Nikodijević, Danijela D.
AU  - Jovankić, Jovana V.
AU  - Cvetković, Danijela M.
AU  - Anđelković, Marko
AU  - Nikezić, Aleksandra G.
AU  - Milutinović, Milena G.
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0014299921006208
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4481
AB  - This study evaluated the potential of antitumor activity of snake venom from Vipera ammodytes and L-amino acid oxidase from Crotalus adamanteus on different colorectal cancer cell lines through determination of cytotoxic activity by MTT assay, pro-apoptotic activity by acridine orange/ethidium bromide staining, and concentrations of redox status parameters (superoxide, reduced glutathione, lipid peroxidation) by colorimetric methods. The expression of genes involved in the biotransformation process and metabolite efflux was determined by qPCR method, while protein expression of glutathione synthetase and P-glycoprotein were analysed by immunocytochemistry. The analysis of cell death shows that snake venom dominantly leads cells to necrosis. Induction of apoptosis by L-amino acid oxidase was in correlation with oxidative disbalance in cancer cells. Gene expression profile of membrane transporters and CYP genes were different in each cell line and in correlation with their sensitivity of treatment. Our results show that L-amino acid oxidase from snake venom is a potent cytotoxic substance with pronounced pro-apoptotic activity. The inhibition of P-glycoprotein suggests that L-amino acid oxidase is a good substance for furter research of antitumor effect, with unexpressed potential for occurrence of drug resistance in vitro.
PB  - Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.
VL  - 910
DO  - 10.1016/j.ejphar.2021.174466
SP  - 174466
ER  - 

@article{
author = "Nikodijević, Danijela D. and Jovankić, Jovana V. and Cvetković, Danijela M. and Anđelković, Marko and Nikezić, Aleksandra G. and Milutinović, Milena G.",
year = "2021",
abstract = "This study evaluated the potential of antitumor activity of snake venom from Vipera ammodytes and L-amino acid oxidase from Crotalus adamanteus on different colorectal cancer cell lines through determination of cytotoxic activity by MTT assay, pro-apoptotic activity by acridine orange/ethidium bromide staining, and concentrations of redox status parameters (superoxide, reduced glutathione, lipid peroxidation) by colorimetric methods. The expression of genes involved in the biotransformation process and metabolite efflux was determined by qPCR method, while protein expression of glutathione synthetase and P-glycoprotein were analysed by immunocytochemistry. The analysis of cell death shows that snake venom dominantly leads cells to necrosis. Induction of apoptosis by L-amino acid oxidase was in correlation with oxidative disbalance in cancer cells. Gene expression profile of membrane transporters and CYP genes were different in each cell line and in correlation with their sensitivity of treatment. Our results show that L-amino acid oxidase from snake venom is a potent cytotoxic substance with pronounced pro-apoptotic activity. The inhibition of P-glycoprotein suggests that L-amino acid oxidase is a good substance for furter research of antitumor effect, with unexpressed potential for occurrence of drug resistance in vitro.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.",
volume = "910",
doi = "10.1016/j.ejphar.2021.174466",
pages = "174466"
}

Nikodijević, D. D., Jovankić, J. V., Cvetković, D. M., Anđelković, M., Nikezić, A. G.,& Milutinović, M. G.. (2021). L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.. in European Journal of Pharmacology
Elsevier B.V.., 910, 174466.
https://doi.org/10.1016/j.ejphar.2021.174466

Nikodijević DD, Jovankić JV, Cvetković DM, Anđelković M, Nikezić AG, Milutinović MG. L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.. in European Journal of Pharmacology. 2021;910:174466.
doi:10.1016/j.ejphar.2021.174466 .

Nikodijević, Danijela D., Jovankić, Jovana V., Cvetković, Danijela M., Anđelković, Marko, Nikezić, Aleksandra G., Milutinović, Milena G., "L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells." in European Journal of Pharmacology, 910 (2021):174466,
https://doi.org/10.1016/j.ejphar.2021.174466 . .

TY  - JOUR
AU  - Milutinović, Milena G.
AU  - Maksimović, Vuk M.
AU  - Cvetković, Danijela M.
AU  - Nikodijević, Danijela D.
AU  - Stanković, Milan S.
AU  - Pešić, Milica
AU  - Marković, Snežana D.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0378874119303010?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3406
AB  - ETHNOPHARMACOLOGICAL RELEVANCE Teucrum chamaedrys L. is one of the known medicinal plants, useful for treatment of various health problems, especially digestive. In this study, we investigated methanol, ethyl-acetate and acetone extracts of T. chamaedrys in respect to their anticancer properties in SW480 colorectal cancer cells. MATERIALS AND METHODS Cytotoxicity and proapoptotic potential were assessed by MTT cell viability assay and AO/EB double staining. Molecular mechanisms of induced apoptosis were determined by monitoring Fas receptor protein expression through immunofluorescence, Caspase 8 and 9 activity, as well as concentrations of O2.- spectrophotometrically. Additionally, mRNA expression of biotransformation enzymes (CYP1A1, CYP1B1, GSTP1) and membrane transporters (MRP1 and MRP2) involved in drug resistance were investigated by qPCR method. Qualitative analysis of individual phenolic compounds was performed by reversed phase HPLC-MS analysis. RESULTS Methanol extract shows the best cytotoxicity and selectivity compared to ethyl-acetate and acetone extracts, mainly causing apoptosis of SW480 cells, without affecting normal HaCaT keratinocytes. The increased expression of Fas receptor protein and caspase 8 activity indicate that the death receptor-mediated pathway plays a crucial role in the observed apoptosis. The increased caspase 9 activity and O2.- concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 in SW480 cells. CONCLUSIONS Induction of apoptosis and inhibition of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 mRNA expression implies that T. chamaedrys can serve as a valuable source of bioactive compounds as dietary supplements or selective anticancer agents, with the ability to induce apoptosis and modulate drug resistance in colorectal cancer cells.
T2  - Journal of Ethnopharmacology
T1  - Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells.
VL  - 240
DO  - 10.1016/j.jep.2019.111951
SP  - 111951
ER  - 

@article{
author = "Milutinović, Milena G. and Maksimović, Vuk M. and Cvetković, Danijela M. and Nikodijević, Danijela D. and Stanković, Milan S. and Pešić, Milica and Marković, Snežana D.",
year = "2019",
abstract = "ETHNOPHARMACOLOGICAL RELEVANCE Teucrum chamaedrys L. is one of the known medicinal plants, useful for treatment of various health problems, especially digestive. In this study, we investigated methanol, ethyl-acetate and acetone extracts of T. chamaedrys in respect to their anticancer properties in SW480 colorectal cancer cells. MATERIALS AND METHODS Cytotoxicity and proapoptotic potential were assessed by MTT cell viability assay and AO/EB double staining. Molecular mechanisms of induced apoptosis were determined by monitoring Fas receptor protein expression through immunofluorescence, Caspase 8 and 9 activity, as well as concentrations of O2.- spectrophotometrically. Additionally, mRNA expression of biotransformation enzymes (CYP1A1, CYP1B1, GSTP1) and membrane transporters (MRP1 and MRP2) involved in drug resistance were investigated by qPCR method. Qualitative analysis of individual phenolic compounds was performed by reversed phase HPLC-MS analysis. RESULTS Methanol extract shows the best cytotoxicity and selectivity compared to ethyl-acetate and acetone extracts, mainly causing apoptosis of SW480 cells, without affecting normal HaCaT keratinocytes. The increased expression of Fas receptor protein and caspase 8 activity indicate that the death receptor-mediated pathway plays a crucial role in the observed apoptosis. The increased caspase 9 activity and O2.- concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 in SW480 cells. CONCLUSIONS Induction of apoptosis and inhibition of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 mRNA expression implies that T. chamaedrys can serve as a valuable source of bioactive compounds as dietary supplements or selective anticancer agents, with the ability to induce apoptosis and modulate drug resistance in colorectal cancer cells.",
journal = "Journal of Ethnopharmacology",
title = "Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells.",
volume = "240",
doi = "10.1016/j.jep.2019.111951",
pages = "111951"
}

Milutinović, M. G., Maksimović, V. M., Cvetković, D. M., Nikodijević, D. D., Stanković, M. S., Pešić, M.,& Marković, S. D.. (2019). Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells.. in Journal of Ethnopharmacology, 240, 111951.
https://doi.org/10.1016/j.jep.2019.111951

Milutinović MG, Maksimović VM, Cvetković DM, Nikodijević DD, Stanković MS, Pešić M, Marković SD. Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells.. in Journal of Ethnopharmacology. 2019;240:111951.
doi:10.1016/j.jep.2019.111951 .

Milutinović, Milena G., Maksimović, Vuk M., Cvetković, Danijela M., Nikodijević, Danijela D., Stanković, Milan S., Pešić, Milica, Marković, Snežana D., "Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells." in Journal of Ethnopharmacology, 240 (2019):111951,
https://doi.org/10.1016/j.jep.2019.111951 . .